G1896A Precore Mutation and Association With HBeAg Status, Genotype and Clinical Status in Patients With Chronic Hepatitis B

BACKGROUND: Precore stop codon (G1896A) mutation is one of the commonest mutations found in patients with chronic hepatitis B. However, over the years, this mutation was not reported much in Malaysia. OBJECTIVES: We therefore investigated the presence of G1896A mutation in Malaysian population and its association with HBeAg status, clinical stage, hepatitis B virus (HBV) genotype and e-seroconversion rate. PATIENTS AND METHODS: Serum samples from 93 patients confirmed as hepatitis B carriers were collected for molecular assay. The whole genome of HBV was amplified by polymerase chain reaction and directly sequenced. The precore and basal core promoter regions were analyzed for presence of mutations. RESULTS: The most commonly observed mutation in the precore region was C1858T with 64.5% prevalence. The precore mutation of interest (G1896A) was identified in 25.8% of isolates. The basal core promoter mutations detected were A1762T-G1764A (26.9%), C1653T (8.6%), A1752G (10.8%) and C1766T (2.2%). No significant association was observed between G1896A mutation and HBeAg-negativity. Nonetheless, G1896A was highly prevalent among HBV genotype B. Clinical association revealed that subjects with G1896A mutations were mainly detected in asymptomatic chronic hepatitis B (58.3%) and liver cirrhosis (41.7%). One subject was diagnosed with fulminant hepatitis (4.2%) and 8.3% had hepatocellular carcinoma (HCC). CONCLUSIONS: Our data suggested an intermediate prevalence of G1896A mutation among Malaysian hepatitis B carriers. The stop codon mutation has a significant association with genotype B and patients with chronic hepatitis B and liver cirrhosis.